Down syndrome, or trisomy 21, occurs when an individual inherits three copies of chromosome 21. Trisomy 21 is the most common chromosomal abnormality, occurring with an incidence of approximately 1 in 750 live births (1). The molecular pathogenesis of this condition is unclear and no direct genotype-phenotype associations have been established. This abnormality leads to the development of complex clinical features and symptoms, including: mental retardation, Alzheimer's disease, seizures, thyroid disorders, cardiac defects, an increased risk of leukemia, infertility, gastrointestinal defects and early aging (2). The risk of trisomy 21 increases with advanced maternal age, when an abnormal parental karyotype is present and with history of having another child or previous pregnancy with Down syndrome (3).
Current screening methods for trisomy 21 incorporate a physical marker with markers found in maternal serum. The physical marker, fetal nuchal translucency (NT), is measured by ultrasound. Serum markers, pregnancy-associated plasma protein A (PAPP-A) and human chorionic gonadotropin beta (β-hCG) are measured in maternal serum during the first trimester. Alpha fetoprotein (AFP), unconjugated estriol (uE3), β-hCG and inhibin A are measured in maternal serum during the second trimester. These combined markers have a detection rate of 90-95% with a 5% false positive rate (4). The screening markers which are currently available are not ideal. They require first and second trimester procedures and they offer relatively low specificity, producing many false positive results which require invasive follow-up by amniocentesis (4).